DESCRIPTION: This proposal is to continue studies on the molecular properties of two members of the heat shock factor (HSF) family and to identify the upstream signals involved in the cellular stress response. The inducible transcription of heat shock genes is mediated by the activities of a family of HSFs. HSF1 and HSF2 are the foci of this proposal. HSF1 is the major stress-responsive transcription factor activated by heat shock, oxidative stress, heavy metals, and other forms of physiological stress, whereas HSF2 is a closely related factor whose activities are activated by distinct conditions including early murine development and differentiation. The goals of the proposed studies are to understand how the activities of a family of heat shock transcription factors (HSFs) are regulated in response to diverse environmental and physiological conditions that modulate the transcription of genes encoding heat shock proteins and molecular chaperons.